GDF8_PIG
ID GDF8_PIG Reviewed; 375 AA.
AC O18831; Q540D6;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Growth/differentiation factor 8;
DE Short=GDF-8;
DE AltName: Full=Myostatin;
DE Flags: Precursor;
GN Name=MSTN; Synonyms=GDF8;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=9356471; DOI=10.1073/pnas.94.23.12457;
RA McPherron A.C., Lee S.-J.;
RT "Double muscling in cattle due to mutations in the myostatin gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:12457-12461(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15986890; DOI=10.1007/bf02879670;
RA Yu Z., Li Y., Meng Q., Yuan J., Zhao Z., Li W., Hu X., Yan B., Fan B.,
RA Yu S., Li N.;
RT "Comparative analysis of the pig BAC sequence involved in the regulation of
RT myostatin gene.";
RL Sci. China, Ser. C, Life Sci. 48:168-180(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Duroc, Hampshire, Meishan, and Yorkshire; TISSUE=Skeletal muscle;
RA Voelker G.R., Conroy J.C., Wheeler M.B.;
RT "Porcine myostatin cDNA sequences: Duroc, Hampshire, Meishan and Yorkshire
RT pigs.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Landrace, Large white, Meishan, and Pietrain;
RA Stinckens A., Luyten T., Bijttebier J., Van den Maagdenberg K.,
RA Dieltiens D., Janssens S., De Smet S., Georges M., Buys N.;
RT "Characterization of the porcine MSTN gene in different pig breeds.";
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-10, AND NUCLEOTIDE SEQUENCE [MRNA]
RP OF 36-375.
RC TISSUE=Muscle;
RA Daneau I., Silversides D.W.;
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Acts specifically as a negative regulator of skeletal muscle
CC growth. {ECO:0000250|UniProtKB:O08689}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with WFIKKN2, leading
CC to inhibit its activity. Interacts with FSTL3.
CC {ECO:0000250|UniProtKB:O08689}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:O08689}.
CC -!- PTM: Synthesized as large precursor molecule that undergoes proteolytic
CC cleavage to generate an N-terminal propeptide and a disulfide linked C-
CC terminal dimer, which is the biologically active molecule. The
CC circulating form consists of a latent complex of the C-terminal dimer
CC and other proteins, including its propeptide, which maintain the C-
CC terminal dimer in a latent, inactive state. Ligand activation requires
CC additional cleavage of the prodomain by a tolloid-like
CC metalloproteinase. {ECO:0000250|UniProtKB:O08689}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; AF019623; AAB86690.1; -; mRNA.
DR EMBL; AY208121; AAO31983.1; -; Genomic_DNA.
DR EMBL; AF188635; AAF02770.1; -; mRNA.
DR EMBL; AF188636; AAF02771.1; -; mRNA.
DR EMBL; AF188637; AAF02772.1; -; mRNA.
DR EMBL; AF188638; AAF02773.1; -; mRNA.
DR EMBL; EF490986; ABO64638.1; -; Genomic_DNA.
DR EMBL; EF490987; ABO64639.1; -; Genomic_DNA.
DR EMBL; EF490988; ABO64640.1; -; Genomic_DNA.
DR EMBL; EF490989; ABO64641.1; -; Genomic_DNA.
DR EMBL; EF490990; ABO64642.1; -; Genomic_DNA.
DR EMBL; AF033855; AAC08035.1; -; mRNA.
DR EMBL; AF093798; AAC62489.1; -; Genomic_DNA.
DR AlphaFoldDB; O18831; -.
DR SMR; O18831; -.
DR STRING; 9823.ENSSSCP00000017001; -.
DR PaxDb; O18831; -.
DR PeptideAtlas; O18831; -.
DR PRIDE; O18831; -.
DR Ensembl; ENSSSCT00000017472; ENSSSCP00000017001; ENSSSCG00000016047.
DR Ensembl; ENSSSCT00015002832; ENSSSCP00015000900; ENSSSCG00015002286.
DR Ensembl; ENSSSCT00025067980; ENSSSCP00025029196; ENSSSCG00025049835.
DR Ensembl; ENSSSCT00030023330; ENSSSCP00030010461; ENSSSCG00030016859.
DR Ensembl; ENSSSCT00035037306; ENSSSCP00035014874; ENSSSCG00035028194.
DR Ensembl; ENSSSCT00040025633; ENSSSCP00040010829; ENSSSCG00040018971.
DR Ensembl; ENSSSCT00045018814; ENSSSCP00045012947; ENSSSCG00045011070.
DR Ensembl; ENSSSCT00050016408; ENSSSCP00050006740; ENSSSCG00050012141.
DR Ensembl; ENSSSCT00055042989; ENSSSCP00055034200; ENSSSCG00055021878.
DR Ensembl; ENSSSCT00060094644; ENSSSCP00060040929; ENSSSCG00060069269.
DR Ensembl; ENSSSCT00065034252; ENSSSCP00065014182; ENSSSCG00065025598.
DR Ensembl; ENSSSCT00070018169; ENSSSCP00070015094; ENSSSCG00070009359.
DR VGNC; VGNC:96320; MSTN.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000160657; -.
DR HOGENOM; CLU_020515_6_1_1; -.
DR InParanoid; O18831; -.
DR OMA; QICVYIY; -.
DR TreeFam; TF318514; -.
DR Proteomes; UP000008227; Chromosome 15.
DR Proteomes; UP000314985; Chromosome 15.
DR Bgee; ENSSSCG00000016047; Expressed in skeletal muscle tissue and 16 other tissues.
DR ExpressionAtlas; O18831; baseline and differential.
DR Genevisible; O18831; SS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:Ensembl.
DR GO; GO:0014839; P:myoblast migration involved in skeletal muscle regeneration; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0033673; P:negative regulation of kinase activity; IEA:Ensembl.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
DR GO; GO:2000818; P:negative regulation of myoblast proliferation; ISS:AgBase.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:1902725; P:negative regulation of satellite cell differentiation; ISS:AgBase.
DR GO; GO:1902723; P:negative regulation of skeletal muscle satellite cell proliferation; ISS:AgBase.
DR GO; GO:0048632; P:negative regulation of skeletal muscle tissue growth; IEA:Ensembl.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; ISS:UniProtKB.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISS:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR015616; GDF_8.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR001111; TGF-b_propeptide.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR PANTHER; PTHR11848:SF150; PTHR11848:SF150; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Cytokine; Disulfide bond; Glycoprotein;
KW Growth factor; Heparin-binding; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..266
FT /evidence="ECO:0000255"
FT /id="PRO_0000033960"
FT CHAIN 267..375
FT /note="Growth/differentiation factor 8"
FT /id="PRO_0000033961"
FT SITE 98..99
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:O08689"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 272..282
FT /evidence="ECO:0000250|UniProtKB:O14793"
FT DISULFID 281..340
FT /evidence="ECO:0000250|UniProtKB:O14793"
FT DISULFID 309..372
FT /evidence="ECO:0000250|UniProtKB:O14793"
FT DISULFID 313..374
FT /evidence="ECO:0000250|UniProtKB:O14793"
FT DISULFID 339
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:O14793"
SQ SEQUENCE 375 AA; 42791 MW; 0F658685EFDA3418 CRC64;
MQKLQIYVYI YLFMLIVAGP VDLNENSEQK ENVEKEGLCN ACMWRQNTKS SRLEAIKIQI
LSKLRLETAP NISKDAIRQL LPKAPPLREL IDQYDVQRDD SSDGSLEDDD YHATTETIIT
MPTESDLLMQ VEGKPKCCFF KFSSKIQYNK VVKAQLWIYL RPVKTPTTVF VQILRLIKPM
KDGTRYTGIR SLKLDMNPGT GIWQSIDVKT VLQNWLKQPE SNLGIEIKAL DENGHDLAVT
FPGPGEDGLN PFLEVKVTDT PKRSRRDFGL DCDEHSTESR CCRYPLTVDF EAFGWDWIIA
PKRYKANYCS GECEFVFLQK YPHTHLVHQA NPRGSAGPCC TPTKMSPINM LYFNGKEQII
YGKIPAMVVD RCGCS
